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Formation of the Δ 18,19 Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
Author(s) -
Jiang Chunyan,
Qi Zhen,
Kang Qianjin,
Liu Jing,
Jiang Ming,
Bai Linquan
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201503561
Subject(s) - chemistry , methyltransferase , in vivo , enzyme , stereochemistry , catalysis , cofactor , salinomycin , biochemistry , in vitro , biosynthesis , biology , methylation , genetics , gene , antibiotics
Salinomycin is a widely used polyether coccidiostat and was recently found to have antitumor activities. However, the mechanism of its biosynthesis remained largely speculative until now. Reported herein is the identification of an unprecedented function of SlnM, homologous to O ‐methyltransferases, by correlating its activity with the formation of the Δ 18,19 double bond and bis(spiroacetal). Detailed in vivo and in vitro investigations revealed that SlnM, using positively charged S ‐adenosylmethionine (SAM) or sinefungin as the cofactor, catalyzed the spirocyclization‐coupled dehydration of C19 in a highly atypical fashion to yield salinomycin.